本人承担的上一个国家自然科学基金项目的研究结果显示：“肾主骨”存在性别差异，不同性别之间，Wnt成骨细胞调控通路和OPG/RANKL破骨细胞调控通路发生不同改变，是造成这种差异的机理之一。研究表明，PI3K/Akt信号通路分别是Wnt成骨细胞调控通路和OPG/RANKL破骨细胞调控通路的下游通路，在调控成骨细胞和破骨细胞分化、增殖和活性方面发挥着重要作用，是使骨骼进行正常代谢的关键调控通路之一。据此推测，不同性别之间，成骨细胞和破骨细胞PI3K/Akt信号通路发生进一步的不同改变，可能是导致“肾主骨”存在性别差异的更深入的机制之一。基于此，本项目拟采用动物实验与细胞培养相结合的方法，进一步从成骨细胞与破骨细胞PI3K/Akt信号通路角度，深入探讨“肾主骨”性别差异的机理。本研究将有助于进一步阐明 “肾主骨” 理论的科学内涵，并可为针对不同性别骨质疏松症患者进行遣方用药提供实验依据。

Strong evidence has been detected that there exist “gender differences” during the biological procedure of “kidney governing bone” in our previous project from National Natural Science Foundation of China, Wnt osteoblast regulation pathways and OPG/RANKL osteoclast regulation pathways were indicated to change in different ways in male and female objects. PI3K/Akt signaling pathways are the downstream pathways of Wnt osteoblast regulation and OPG/RANKL osteoclast regulation pathways, respectively, they play the essential roles in regulating the differentiation, proliferation and activity of osteoblast and osteoclast, thus to have great impact in normal bone metabolism. Consequently, the different gender-related changes in osteoblast and osteoclast PI3K/Akt signaling pathways might be responsible for the in-depth mechanisms of the gender differences in “kidney governing bone” procedure. Therefore, in this study we plan to develop the animal experiments combing with cell culture methods to further explore the mechanisms underlying the gender differences in the “kidney governing bone" procedure based on osteoblast and osteoclast PI3K/Akt signaling pathways. The outcomes will certainly facilitate to decipher the mechanisms of the “kidney governing bone” theory in Chinese medicine as well as to provide the experimental supports for the individualized prescription in osteoporosis patients based on gender difference.